Abstract Leishmaniasis, a widely prevalent disease throughout tropical and subtropical regions of the world, is a chronic protozoan infection of humans and mammals that remains grossly underreported and causes significant global morbidity and mortality. Different species of the intracellular protozoan parasites of the genus Leishmania can cause human leishmaniasis, resulting in various visceral, cutaneous, and mucocutaneous manifestations. The risk of leishmaniasis manifesting as a more severe entity is dependent on the infecting parasites’ immune evasion potential. Some causal associations between leishmaniasis and malignancy have been evidenced in experimental animals and humans. Leishmania spp. infection can play a significant, direct or indirect, role in the pathogenesis and prognosis of some malignant disorders through numerous pathophysiologic cascades. Aging, chronic ultraviolet radiation exposure, and popular treatment abuse (eg, chameleon saliva, cactus recipes, corrosive chemicals, and topical steroids) have been proposed as the principal triggering factors. Malignancy should be considered in the differential diagnosis of leishmaniasis in endemic regions, such as Yemen. Understanding this relationship could enrich the provision of early diagnosis, proper management, and prompt control of cancer.